当前共找到 1280 篇文献分享,本页显示第 901 - 920 篇。
901.
张贝
(2022-09-30 18:50):
#paper doi: 10.1038/s41587-020-0548-6. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol. 2020. PICRUSt2是一款基于标记基因序列(通常为16S rRNA)来预测宏基因组功能丰度的软件,本文自2020年发表以来,已被引用近1200次(Google Scholar)。PICRUSt2在原有PICRUSt1版本的基础上进行升级,更新了基因家族和参考基因组数据库(扩大10倍以上),可与任何OTU选择或去噪算法的互操作,并能够进行表型预测。Benchmarking结果表明,PICRUSt2总体上比PICRUSt和其他竞争方法更准确。同时,PICRUSt2还允许添加自定义参考数据库。
IF:33.100Q1
Nature biotechnology,
2020-06.
DOI: 10.1038/s41587-020-0548-6
PMID: 32483366
PMCID:PMC7365738
Abstract:
No abstract available.
902.
Vincent
(2022-09-30 14:56):
#paper doi: https://doi.org/10.1038/s43586-021-00056-9 Genome-wide association studies. Nature Reviews Methods Primers. 2021. GWAS旨在寻找基因型和表型之间的关联。截止目前,总共有超过5700项,涵盖3300性状的GWAS研究。这篇review文章丛统计原理、实验设计、实际操作、结果解释,下游应用等方面很好地介绍了全基因组关联研究(GWAS)。在统计原理方面,文章介绍了假设检验常用的线性混合模型,假发现率的控制(FDR control)和下游fine mapping方法。实验设计方面,文章详细介绍了人群的选择(population-based, family-based 和 isolation populations),以及测序技术(microarray, WES, WGS)方面的优缺点。应用上,文章介绍了GWAS的两大重要应用:疾病风险预测(PRS score) 和 揭示生物性状的遗传基础。文章最后还提及了GWAS研究目前的局限和对未来发展的期待。总结起来是篇很不错的GWAS入门文章。
Abstract:
Genome-wide association studies (GWAS) test hundreds of thousands of genetic variants across many genomes to find those statistically associated with a specific trait or disease. This methodology has generated a …
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Genome-wide association studies (GWAS) test hundreds of thousands of genetic variants across many genomes to find those statistically associated with a specific trait or disease. This methodology has generated a myriad of robust associations for a range of traits and diseases, and the number of associated variants is expected to grow steadily as GWAS sample sizes increase. GWAS results have a range of applications, such as gaining insight into a phenotype’s underlying biology, estimating its heritability, calculating genetic correlations, making clinical risk predictions, informing drug development programmes and inferring potential causal relationships between risk factors and health outcomes. In this Primer, we provide the reader with an introduction to GWAS, explaining their statistical basis and how they are conducted, describe state-of-the art approaches and discuss limitations and challenges, concluding with an overview of the current and future applications for GWAS results.
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903.
大象城南
(2022-09-30 14:31):
#paper doi.org/10.1016/j.neuroimage.2012.12.054 Track-weighted functional connectivity (TW-FC): A tool for characterizing the structural–functional connections in the brain. NeuroImage. 2013. MRI 为无创研究大脑中的功能和结构连接提供了强大的工具。功能连接 (FC) 技术利用缓慢自发信号波动的内在时间相关性来表征大脑功能网络。此外,弥散 MRI 纤维追踪可用于研究白质结构连接。近年来,人们对结合这两种技术以提供大脑的整体结构-功能描述产生了相当大的兴趣。在这项工作中,我们应用了最近提出的超分辨率轨迹加权成像 (TWI) 方法来演示如何将全脑纤维跟踪数据与 FC 数据相结合以生成轨迹加权 (TW) FC 图FC 网络。该方法应用于来自 8 名健康志愿者的数据,并用 ( i ) 使用基于种子连接的分析获得的 FC 网络(在楔前叶/后扣带回皮层,PCC 中播种,已知是默认模式网络的一部分)进行说明,和(二) 使用独立成分分析生成的 FC 网络(特别是默认模式、注意力、视觉和感觉运动网络)。TW-FC 图在连接 FC 网络节点的白质结构中显示出高强度。例如,扣带束在基于 PCC 种子的分析中显示出最强的 TW-FC 值,因为它们在内侧额叶皮层和楔前叶/后扣带皮层之间的连接中起主要作用;类似地,上纵束在注意力网络、视觉网络中的视辐射以及感觉-运动网络中的皮质脊髓束和胼胝体中都有很好的表现。TW-FC 地图突出显示与给定 FC 网络相关的白质连接,并且它们在给定体素中的强度反映了由穿过该体素的结构连接连接的网络节点部分的功能连接性。因此,它们包含与用于生成它们的图像不同的(和新颖的)图像对比度。本研究中显示的结果说明了 TW-FC 方法在将结构和功能数据融合为单一的定量图像。因此,这种技术可以在神经科学和神经学中具有重要的应用,例如基于体素的比较研究。
Abstract:
MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous …
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MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study the white matter structural connections. In recent years, there has been considerable interest in combining these two techniques to provide an overall structural-functional description of the brain. In this work we applied the recently proposed super-resolution track-weighted imaging (TWI) methodology to demonstrate how whole-brain fibre-tracking data can be combined with FC data to generate a track-weighted (TW) FC map of FC networks. The method was applied to data from 8 healthy volunteers, and illustrated with (i) FC networks obtained using a seeded connectivity-based analysis (seeding in the precuneus/posterior cingulate cortex, PCC, known to be part of the default mode network), and (ii) with FC networks generated using independent component analysis (in particular, the default mode, attention, visual, and sensory-motor networks). TW-FC maps showed high intensity in white matter structures connecting the nodes of the FC networks. For example, the cingulum bundles show the strongest TW-FC values in the PCC seeded-based analysis, due to their major role in the connection between medial frontal cortex and precuneus/posterior cingulate cortex; similarly the superior longitudinal fasciculus was well represented in the attention network, the optic radiations in the visual network, and the corticospinal tract and corpus callosum in the sensory-motor network. The TW-FC maps highlight the white matter connections associated with a given FC network, and their intensity in a given voxel reflects the functional connectivity of the part of the nodes of the network linked by the structural connections traversing that voxel. They therefore contain a different (and novel) image contrast from that of the images used to generate them. The results shown in this study illustrate the potential of the TW-FC approach for the fusion of structural and functional data into a single quantitative image. This technique could therefore have important applications in neuroscience and neurology, such as for voxel-based comparison studies.
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904.
尹志
(2022-09-30 11:06):
#paper doi:10.48550/arXiv.1907.10830 U-GAT-IT: Unsupervised Generative Attentional Networks with Adaptive Layer-Instance Normalization for Image-to-Image Translation, ICLR 2020. 这又是一篇图像翻译的文章,还是在网络结构上做了有效的改进。作者通过提出一个新的注意力模块和一种新的归一化函数实现无监督的图像翻译工作。作者提出的注意力模块对于图像的几何形变能够做出很好的处理,这也让文章的架构对于很多艺术风格的变化处理具有优越的效果。
arXiv,
2019.
DOI: 10.48550/arXiv.1907.10830
Abstract:
We propose a novel method for unsupervised image-to-image translation, which incorporates a new attention module and a new learnable normalization function in an end-to-end manner. The attention module guides our …
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We propose a novel method for unsupervised image-to-image translation, which incorporates a new attention module and a new learnable normalization function in an end-to-end manner. The attention module guides our model to focus on more important regions distinguishing between source and target domains based on the attention map obtained by the auxiliary classifier. Unlike previous attention-based method which cannot handle the geometric changes between domains, our model can translate both images requiring holistic changes and images requiring large shape changes. Moreover, our new AdaLIN (Adaptive Layer-Instance Normalization) function helps our attention-guided model to flexibly control the amount of change in shape and texture by learned parameters depending on datasets. Experimental results show the superiority of the proposed method compared to the existing state-of-the-art models with a fixed network architecture and hyper-parameters. Our code and datasets are available at this https URL or this https URL.
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905.
lsj
(2022-09-30 08:58):
#paper DOI:The Journal of Neuroscience, January 1995, 15(l): 70-66
背景:之前的研究已知在postsubiculum中记录到在平面上与动物头朝向功能的神经元,这类神经元的放电独立于动物在环境中的行为和位置。解剖学研究发现postsubiculum和ATN具有双向连接。
目的:为了能够探究大脑中头朝向细胞信号处理,在自由运动的小鼠脑中采用单细胞记录的技术刻画神经元行为和空间的关联。
实验环境:在包含单一朝向线索的圆柱形环境中训练小鼠获取食物。
结论:在ATN中单记录的细胞中大约60%的细胞放电都与平面上头朝向有关。实验中包含朝向线索的旋转表明偏好方向发放朝向可以被显著的视觉线索控制。与postsubicular的HD细胞相比,受抑制动物的被动旋转显示,当动物的头部朝向偏好方向时,大多数ATN的HD细胞停止放电。这些发现证明了ATN中头朝向细胞的存在并且表明这个区域在空间导航方面的潜在重要性。
相关结论:在动物的观察和定量分析中发现头朝向细胞的发放不依赖于动物的行为,位置,线性速度,角头速度或者环境中的位置,这样的细胞大多数在丘脑前背核(anterior dorsal thalamic nucleus)。每个头朝向细胞都有一个偏好方向,在该偏好方向上放电最大,当远离偏好方向时细胞的发放率线性下降。所有的偏好方向覆盖360度。定量分析发现这些细胞与在postsubicular中的HD细胞具有相同的参数值,比如发放率峰值,朝向发放范围。
讨论:头朝向信号的起源是被讨论的,因为postsubiculum和ATN之间具有双向连接的存在,所以下一步的研究进一步探究头朝向信息流。最后ATN中HD细胞和postsubicular中HD细胞有不同之处,在于ATN需要意志的运动输入。
Abstract:
Previous studies have identified neurons in the postsubiculum which discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the …
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Previous studies have identified neurons in the postsubiculum which discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Anatomical studies have shown that the postsubiculum contains reciprocal connections with the anterior thalamic nuclei (ATN). In order to determine how the head direction (HD) cell signal is processed in the brain, single- unit recordings were monitored in the ATN of freely moving rats in order to characterize their behavioral and spatial correlates. Animals were trained to retrieve food pellets thrown randomly into a cylindrical apparatus containing a single orientation cue. Single unit recordings in the ATN showed that approximately 60% of the recorded cells discharged in relation to the animal's head direction in the horizontal plane. Observation of the animal and quantitative analyses showed that HD cell firing was not dependent on the animal's behavior, trunk position, linear speed, angular head velocity, or location in the environment. Most of these cells were localized to the anterior dorsal thalamic nucleus. Each HD cell contained only one head direction at which the cell discharged maximally and the firing rate decreased linearly away from this preferred direction. The preferred firing directions from all cells recorded were distributed over a 360° range. Quantitative analysis showed that these cells contained similar discharge parameters (peak firing rate, directional firing range) to values reported previously for post-subicular HD cells (Taube et el., 1990a). Experiments involving rotation of the orientation cue showed that the preferred firing direction could be controlled by a salient visual cue. In contrast to postsubicular HD cells, passive rotation of a restrained animal showed that most ATN HD cells ceased discharging when the animal's head was oriented in the preferred direction. These findings demonstrate the presence of HD cells in the ATN and indicate the potential importance of this area for spatial navigation. The origin of the head direction signal is discussed and it is concluded that because of the presence of reciprocal connections between the postsubiculum and the ATN, further studies are required in order to determine the direction in which this head-directional information is flowing. Finally, ATN HD cells differ from postsubicular HD cells by appearing to require volitional motoric input.
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906.
xh
(2022-09-30 06:12):
#paper DOI: 10.1038/nature08494 Nature 10/2009 Finding the missing heritability of complex diseases. 本文研究人类疾病中缺失遗传性的潜在来源,并提出了研究策略,包括并超越了目前的全基因组关联方法,以阐明复杂疾病的遗传学,并提高其潜力以实现有效的疾病预防或治疗。
但是对于神经精神疾病方面检测到的变异体的相对缺乏,如自闭症谱系障碍。
Abstract:
Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far …
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Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
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907.
笑对人生
(2022-09-29 20:05):
#paper doi: 10.1038/s41568-021-00431-4. Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer. 2022 Mar;22(3):174-189. 2016年5月18日,来自罗氏的阿替丽珠成为了首个获批上市的PD-L1抑制剂,用于治疗转移性/复发性尿路上皮癌。PD-L1抑制剂能成药的基础是肿瘤的免疫逃逸机制,即肿瘤细胞为了逃避以T细胞为代表的免疫细胞攻击,自身表面会表达PD-L1(又称为CD274或B7-H1),进而与T细胞表面的PD-1相互作用,触发抑制信号,使T细胞无法发挥杀死’‘异己’的功能。PD-L1抑制剂能够有效地结合肿瘤细胞表面的PD-1蛋白,从而恢复T细胞对肿瘤细胞的识别和杀伤。以上所述均是基于细胞外表面的PD-L1分子(cell-extrinsic),然而,有关细胞内的PD-L1信号分子(cell-intrinsic)的研究相对较少且缺乏深入理解。本综述从细胞内PD-L1亚细胞定位、肿瘤细胞内PD-L1免疫调控、影响细胞内PD-L1表达机制以及针对胞内PD-L1潜在治疗策略和生物标志物四个方面作了较为全面总结和讨论。作者认为靶向肿瘤胞内PD-L1可能有助于进一步提高目前免疫治疗的效果,或者作为一种联合策略,最终使更多的癌症患者获益。另外,胞内的PD-L1也是一种有潜力的预后或预测生物标志物。文章中提到的胞内PD-L1包括胞内可溶性PD-L1蛋白、囊泡包裹的PD-L1以及PD-L1蛋白亚基(或异构体)
Abstract:
The paradigm of surface-expressed programmed death ligand 1 (PDL1) signalling to immune cell programmed death 1 (PD1) to inhibit antitumour immunity has helped to develop effective and revolutionary immunotherapies using …
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The paradigm of surface-expressed programmed death ligand 1 (PDL1) signalling to immune cell programmed death 1 (PD1) to inhibit antitumour immunity has helped to develop effective and revolutionary immunotherapies using antibodies blocking these cell-extrinsic interactions. The recent discovery of cancer cell-intrinsic PDL1 signals has broadened understanding of pathologic tumour PDL1 signal consequences that now includes control of tumour growth and survival pathways, stemness, immune effects, DNA damage responses and gene expression regulation. Many such effects are PD1-independent. These insights demonstrate that the prevailing cell-extrinsic PDL1 signalling paradigm is useful, but incomplete in important respects. This Perspective discusses historical and recent advances in understanding cancer cell-intrinsic PDL1 signals, mechanisms for signal controls and important immunopathologic consequences including resistance to cytotoxic agents, targeted small molecules and immunotherapies. Cancer cell-intrinsic PDL1 signals present novel drug discovery targets and also have potential as reliable treatment response biomarkers. Cancer cell-intrinsic PD1 signals and cell-intrinsic PDL1 signals in non-cancer cells are discussed briefly, as are PDL1 signals from soluble and vesicle-bound PDL1 and PDL1 isoforms. We conclude with suggestions for addressing the most pressing challenges and opportunities in this rapidly developing field.
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908.
DeDe宝
(2022-09-29 17:28):
#paper doi: 10.1016/j.intell.2022.101681
Process-oriented intelligence research: A review from the cognitive perspective
2022.09, Intelligence:过程导向的智力研究:从认知的角度进行回顾(综述)
综述回顾了工作记忆、加工速率、执行过程等认知过程与智力差异相关的实证结果,介绍了测量通用机制和过程的认知测量模型,提出了智力理论的启示和发展更多机械智能理论的可能性。作者认为:①智力差异背后的特定认知过程仍然难以捉摸。②平均表现通常无法隔离单个认知过程。③认知过程或机制的正式模型提供了更具体的指标
Abstract:
Despite over a century of research on intelligence, the cognitive processes underlying intelligent behavior are still unclear. In this review, we summarize empirical results investigating the contribution of cognitive processes …
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Despite over a century of research on intelligence, the cognitive processes underlying intelligent behavior are still unclear. In this review, we summarize empirical results investigating the contribution of cognitive processes associated with working memory capacity, processing speed, and executive processes to intelligence differences. Specifically, we (a) evaluate how cognitive processes associated with the three different cognitive domains have been measured, and (b) how these processes are related to individual differences in intelligence. Consistently, this review illustrates that isolating single cognitive processes using average performance in cognitive tasks is hardly possible. Instead, formal models that implement theories of cognitive processes underlying performance in different cognitive tasks may provide more adequate indicators of single cognitive processes. Therefore, we outlined which models for working memory capacity, processing speed, and executive processes may provide more specific insights into cognitive processes associated with individual differences in intelligence. Finally, we discuss implications of a process-oriented intelligence research using cognitive measurement models for psychometric theories of intelligence and argue that a model-based approach might overcome validity problems of traditional intelligence theories.
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909.
前进
(2022-09-29 12:12):
#paper Affine Medical Image Registration with Coarse-to-Fine Vision Transformer Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), 2022, pp. 20835-20844
仿射配准是综合医学图像配准中不可缺少的一部分。然而,关于快速、鲁棒的仿射配准算法的研究很少。这些研究大多都是联合仿射和变形配准的CNN模型,而对仿射子网络的独立性能研究较少。此外,现有的基于CNN的仿射配准方法要么关注输入的局部错位,要么关注输入的全局方向和位置,以预测仿射变换矩阵,这种方法对空间初始化敏感,泛化能力有限。这篇论文提出了一种快速、鲁棒的基于学习的三维仿射医学图像配准算法C2FViT。该方法自然地利用Transformer的全局连通性和CNN的局部性以及多分辨率策略来学习全局仿射配准,并且在3D脑图谱配准中评估了该方法。结果表明该方法在配准精度、鲁棒性、配准速度和泛化性都表现良好。
arXiv,
2022.
DOI: 10.48550/arXiv.2203.15216
Abstract:
Affine registration is indispensable in a comprehensive medical image registration pipeline. However, only a few studies focus on fast and robust affine registration algorithms. Most of these studies utilize convolutional …
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Affine registration is indispensable in a comprehensive medical image registration pipeline. However, only a few studies focus on fast and robust affine registration algorithms. Most of these studies utilize convolutional neural networks (CNNs) to learn joint affine and non-parametric registration, while the standalone performance of the affine subnetwork is less explored. Moreover, existing CNN-based affine registration approaches focus either on the local misalignment or the global orientation and position of the input to predict the affine transformation matrix, which are sensitive to spatial initialization and exhibit limited generalizability apart from the training dataset. In this paper, we present a fast and robust learning-based algorithm, Coarse-to-Fine Vision Transformer (C2FViT), for 3D affine medical image registration. Our method naturally leverages the global connectivity and locality of the convolutional vision transformer and the multi-resolution strategy to learn the global affine registration. We evaluate our method on 3D brain atlas registration and template-matching normalization. Comprehensive results demonstrate that our method is superior to the existing CNNs-based affine registration methods in terms of registration accuracy, robustness and generalizability while preserving the runtime advantage of the learning-based methods. The source code is available at this https URL.
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910.
Spring
(2022-09-28 11:59):
#paper doi: 10.1016/S2666-5247(22)00185-9
The early-life gut microbiome and vaccine efficacy
09-08, Lancet子刊:生命早期肠道菌群与疫苗效力(综述)
① 许多疫苗的效力在不同地区的婴儿间存在很大差异,这与肠道菌群组成差异有关;② 肠道菌群和免疫系统间的互作,以及遗传和环境的影响,可以解释个体间对疫苗免疫反应的差异;③ 双歧杆菌、拟杆菌及其代谢产物具有免疫调节特性,可影响早期免疫接种结果;④ 短链脂肪酸,胞外多糖和细菌细胞外囊泡等微生物产物可以调节宿主的免疫应答;⑤ 对健康婴儿肠菌中的关键菌株及其副产物的进一步了解和定性,可能催生新一代疫苗增强疗法。
Abstract:
Vaccines are one of the greatest successes of public health, preventing millions of cases of disease and death in children each year. However, the efficacy of many vaccines can vary …
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Vaccines are one of the greatest successes of public health, preventing millions of cases of disease and death in children each year. However, the efficacy of many vaccines can vary greatly between infants from geographically and socioeconomically distinct locations. Differences in the composition of the intestinal microbiome have emerged as one of the main factors that can account for variations in immunisation outcomes. In this Review, we assess the influence of the gut microbiota upon early life immunity, focusing on two important members of the microbiota with health-promoting and immunomodulatory properties: Bifidobacterium and Bacteroides. Additionally, we discuss their immune stimulatory microbial properties, interactions with the host, and their effect on vaccine responses and efficacy in infants. We also provide an overview of current microbiota-based approaches to enhance vaccine outcomes, and describe novel microbe-derived components that could lead to safer, more effective vaccines and vaccine adjuvants.
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911.
惊鸿
(2022-09-27 09:09):
#paper doi:Volume 40, Issue 9, 12 September 2022, Pages 999-1009.e6Detection and localization of early- and late-stage cancers using platelet 这篇论文解释了RNA癌症患者受益于早期肿瘤检测,因为治疗结果对不太晚期的癌症更有利。血小板参与癌症进展,被认为是癌症检测的有前途的生物来源,因为它们根据局部和全身线索改变其RNA含量。我们表明,基于肿瘤的血小板(TEP)RNA血液测试能够检测18种癌症类型。血栓形成Seq在无症状对照组的特异性为99%,在I-IV期癌症患者的1,096份血液样本中有三分之二和352名I-III期肿瘤中的一半中正确检测到癌症的存在。对症对照组,包括炎症和心血管疾病以及良性肿瘤,假阳性检测结果增加,平均特异性为78%。此外,血栓形成Seq在超过80%的癌症患者中正确确定了五种不同肿瘤类型的肿瘤起源部位。这些结果突出了TEP衍生的RNA组合的潜在特性,以补充当前基于血液的癌症筛查方法。
Abstract:
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for …
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Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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912.
颜林林
(2022-09-26 23:20):
#paper doi:10.1002/ajmg.a.62974 American Journal of Medical Genetics, 2022, Reduced resource utilization with early use of next-generation sequencing in rare genetic diseases in an Asian cohort. 这篇来自新加坡的文章,回顾了一家三级医院从2004到2020年的患者数据,调取其做过遗传检测且有相应计费数据的病例,最终筛选出近百例罕见病患者,覆盖GDD(全身发育迟缓)、MCA(多发性先天异常)、NMD(神经肌肉疾病)和 PID(原发性免疫缺陷)四种遗传疾病。根据他们病历中记录的所做检测内容,结合医疗常规实践路径规范,评价按照规范依次进行多种不同检测、对比合理去掉其中一个或多个检测项目,直至只留下最终采取全外显子组测序(WES)的策略。分别进行经济学和检测准确性方面的评估,由此给出一些实践建议。虽然病例收集时间跨度长,但最终可用病例数仍然有限,其结果价值也因此受到影响。不过该文章思路挺值得学习的,对于推动将WES或WGS(全基因组测序)提升至一线或早期的诊断方法,是一个合理且有说服力的策略。若在中国这样一个人口基数大的国家,建设并长期详细记录诊疗数据,用于此类回顾研究的开展,将是价值更加巨大的。
Abstract:
Children with genetic diseases endure a prolonged and costly "diagnostic odyssey." The use of whole exome sequencing (WES) and whole genome sequencing (WGS) has improved the diagnosis rate, ending the …
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Children with genetic diseases endure a prolonged and costly "diagnostic odyssey." The use of whole exome sequencing (WES) and whole genome sequencing (WGS) has improved the diagnosis rate, ending the odyssey. However, the additional costs associated WES/WGS has impeded their adoption in Asian settings. We aim to estimate the expected change to the mean number of diagnostic tests used, and the associated costs from a decision to use WES early in the diagnostic pathways of pediatric phenotypes, as compared to Existing Practice. Retrospective data from a patient cohort recruited under the Singapore Undiagnosed Disease Program from a tertiary hospital in Singapore, for the period October 2004 to September 2020, was analyzed. Four phenotype-specific subgroups were used: multiple congenital anomalies (MCA) without developmental delay; global developmental delay (GDD); neuromuscular disorder (NMD) and primary immunodeficiency disorder (PID). Patients had undergone a traditional diagnostic pathway and received a diagnosis either through clinical exome or WES or WGS. A costs only analysis was performed, by tabulating the outcomes "test quantity" and "test costs" incurred by patients. The outcomes were compared with alternate diagnostic pathways which incorporates the early introduction of WES trio testing. To include uncertainty in cost outcomes, simulation studies were done on uncertain parameters. Cost outcomes are reported in Singapore dollars (S$). The 92 included patients had MCA (n = 48), GDD (n = 29), NMD (n = 10), or PID (n = 5). Patients were aged between 18 days and 26 years, 52.2% were males. The majority were of Chinese ethnicity (81.5%). If patients had access to WES directly, test quantity reduced by 97.38% for MCA, 96.98% for GDD, 96.56% for NMD, and 99.84% for PID. The expected cost savings per patient were $5940 for MCA (US$4433), $5342 for GDD (US$3986), $4622 for NMD (US$3449), and $58,497 for PID (US$43,654). Uncertainty assessment for MCA and GDD patients showed a respective likelihood of 86.9% and 97.4% for cost savings. Adoption of alternate diagnostic pathways with early WES in selected pediatric subgroups are likelt to reduce costs, when compared to Existing Practice. Benefits arising from earlier diagnosis, and the potential cost savings could mitigate the large initial cost of implementing WES in Asian settings.
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913.
na na na
(2022-09-26 22:58):
#paper doi: 10.1038/nrg.2016.67 Nat Rev Genet, 2016, Computational genomics tools for dissecting tumour-immune cell interactions. 分享一篇比较早的16年综述,本文全方面收录了研究肿瘤免疫中各个环节涉及到的热点软件工具和数据库,描述了基于基因表达谱、DNA甲基化谱和免疫组织化学等分子信息的多种来源和可用于研究肿瘤免疫表型的生信算法,并且深入浅出的讲述了肿瘤免疫相关的技术发展现况、面临的挑战、现今研究重点、未来发展,既可帮助入门学习肿瘤免疫,也可用于深入肿瘤免疫相关研究。虽然时间有点久了,但其中讲述的观点和算法工具至今依然受用。
Abstract:
Recent breakthroughs in cancer immunotherapy and decreasing costs of high-throughput technologies have sparked intensive research into tumour-immune cell interactions using genomic tools. The wealth of the generated data and the …
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Recent breakthroughs in cancer immunotherapy and decreasing costs of high-throughput technologies have sparked intensive research into tumour-immune cell interactions using genomic tools. The wealth of the generated data and the added complexity pose considerable challenges and require computational tools to process, to analyse and to visualize the data. Recently, various tools have been developed and used to mine tumour immunologic and genomic data effectively and to provide novel mechanistic insights. Here, we review computational genomics tools for cancer immunology and provide information on the requirements and functionality in order to assist in the selection of tools and assembly of analytical pipelines.
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914.
李翛然
(2022-09-26 21:03):
#paper doi: 10.1097/01.prs.0000436812.73412.a4 The embrace Device Significantly Decreases Scarring following Scar Revision Surgery in a Randomized Controlled Trial 这篇文章是上一篇(https://paper-hub.cn/xiangma/paper/430)的引用,主要是想看看医美的产品应用。没想到今年我们做了一些实验后,最近有个大发现,联合我们的生发蛋白及配合其中的胶原蛋白成型机制,可以甚至刺激烧伤病人的恢复后的毛囊分化。 这是个大事。下面的工作是具体的试验和基因编辑模型来看看验证一下猜测。
最近连续推荐是因为我们的药物 找到了新的联合用药和适应症方向!并且是一个前沿性靶点!我们一定要做透!
IF:3.200Q1
Plastic and reconstructive surgery,
2014-Feb.
DOI: 10.1097/01.prs.0000436812.73412.a4
PMID: 24469172
Abstract:
No abstract available.
915.
颜林林
(2022-09-25 15:32):
#paper doi:10.1101/2022.09.20.22280143 medRxiv, 2022, Whole-Genome Promoter Profiling of Plasma Cell-Free DNA Exhibits Predictive Value for Preterm Birth. 这篇文章试图从孕期母亲外周血cfDNA中发现早产相关生物标志物。对20例足月与20例早产的入组孕产妇进行全基因组测序,以及相应胎盘和外周血的全转录组测序,从中找到差异表达基因,并与外周血cfDNA中相应基因上游调控序列的覆盖深度进行关联,由此得到的特征,在2590例孕产妇(2072足月对518早产)的NIPT数据中进行验证,并预期此检测将为当前NIPT服务提供更多附加价值。这是一篇预发表文章,其摘要仅仅提及最后的两千多例的模型及性能,与正文整体逻辑还是有一定区别的,显然其文章逻辑还需要再继续打磨,不过这套数据及结果还是挺值得关注下的。
medRxiv,
2022.
DOI: 10.1101/2022.09.20.22280143
Abstract:
Preterm birth (PTB) occurs in around 11% of all births worldwide, resulting in significant morbidity and mortality for both mothers and offspring. Identification of pregnancies at risk of preterm birth …
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Preterm birth (PTB) occurs in around 11% of all births worldwide, resulting in significant morbidity and mortality for both mothers and offspring. Identification of pregnancies at risk of preterm birth in early pregnancy may help improve intervention and reduce its incidence. However, there exist few methods for PTB prediction developed with large sample size, high throughput screening and validation in independent cohorts. Here, we established a large scale, multi center, and case control study that included 2,590 pregnancies (2,072 full term and 518 preterm pregnancies) from three independent hospitals to develop a preterm birth classifier. We implemented whole genome sequencing on their plasma cfDNA and then their promoter profiling (read depth spanning from -1 KB to +1 KB around the transcriptional start site) was analyzed. Using three machine learning models and two feature selection algorithms, classifiers for predicting preterm delivery were developed. Among them, a classifier based on the support vector machine model and backward algorithm, named PTerm (Promoter profiling classifier for preterm prediction), exhibited the largest AUC value of 0.878 (0.852-0.904) following LOOCV cross validation. More importantly, PTerm exhibited good performance in three independent validation cohorts and achieved an overall AUC of 0.849 (0.831-0.866). Taken together, PTerm could be based on current noninvasive prenatal test (NIPT) data without changing its procedure or adding detection cost, which can be easily adapted for preclinical tests.
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916.
颜林林
(2022-09-23 22:56):
#paper doi:10.1371/journal.pgen.1010404 PLOS Genetics, 2022, Analysis of low-level somatic mosaicism reveals stage and tissue-specific mutational features in human development. 这篇文章纳入了来自190人的498个样本,包括神经疾病患者、脑肿瘤患者和健康对照,样本类型包括外周血及脑、心脏、肝脏等组织,对这些样本进行配对的全外显子测序(平均深度~500x),研究各样本的体细胞突变,以及它们在不同组织类型和不同发育阶段的分布情况,以及突变特征差异。对这些突变,还采取Sanger和靶向扩增超高深度测序等方法进行验证,对于突变在不同类型细胞的分布,也使用了流式细胞术进行了验证。分析方法上都比较常规,但作为一套数百例不同组织部位的深度全外显子数据,以及它所描述的体细胞突变的分布,还是比较有重分析挖掘的价值的。
Abstract:
Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of …
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Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.
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917.
徐炳祥
(2022-09-22 22:58):
#paper doi: 10.1186/s13059-022-02757-0 Genome Biology, 2022, Genetic regulation of RNA splicing in human pancreatic islets。在胰岛细胞中存在的非编码编译影响了细胞转录组,从而在I型和II型糖尿病发病过程中可能扮演重要角色。本文在由399名患者组成的队列中分析了一类特殊的常见基因组变异(sQTL,splicing QTL,那些能可变剪接事件的QTL)。sQTL 的靶基因不同于eQTL,暗示着两类QTL可能独立发挥作用。作者识别了一批新的与sQTL关联的I型和II型糖尿病风险基因。作者据此认为胰岛细胞中的可变剪接事件是重要的糖尿病风险因素。
IF:10.100Q1
Genome biology,
2022-09-15.
DOI: 10.1186/s13059-022-02757-0
PMID: 36109769
PMCID:PMC9479353
人胰岛 RNA 剪接的遗传调控
Abstract:
BACKGROUND: Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 …
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BACKGROUND: Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.RESULTS: We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3.CONCLUSIONS: These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.
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背景: 影响胰岛基因转录的非编码遗传变异在 2 型糖尿病 (T2D) 的易感性中起主要作用,也可能导致 1 型糖尿病 (T1D) 风险。然而,对于许多基因座,非编码变异影响糖尿病易感性的机制尚不清楚。
结果: 我们检查了 399 例人类供体胰岛中的剪接 QTL (sQTL),并观察到常见的遗传变异对在胰岛生物学和糖尿病中具有成熟作用的基因剪接具有广泛影响。同时,我们分析表达 QTL (eQTL) 并使用转录组范围的关联以及遗传共定位研究将胰岛 sQTL 或 eQTL 分配给 T2D 和 T1D 易感信号,其中许多信号缺乏候选效应基因。该分析揭示了生物学上合理的机制,包括 T2D 与 sQTL 的关联,该 sQTL 在 ERO1B 中产生无义亚型,ERO1B 是 ER 应激和胰岛素原生物合成的调节因子。扩展的 T2D 风险效应基因列表揭示了过度表达的通路,包括 G 蛋白介导的 cAMP 产生的调节因子。sQTL 的分析还揭示了 T1D 易感性的候选效应基因,例如 DCLRE1B、衰老调节因子和 lncRNA MEG3。
结论: 这些数据揭示了常见遗传变异对胰岛 RNA 剪接的广泛影响。结果支持剪接变异在糖尿病易感性中的作用,并提供了一组具有潜在治疗益处的新遗传靶点。
918.
张浩彬
(2022-09-21 11:01):
#paper https://doi.org/10.48550/arXiv.2106.00750
Unsupervised Representation Learning for Time Series with Temporal Neighborhood Coding
21年ICLR论文,时间序列对比学习
代码:https://github.com/sanatonek/TNC_ representation_learning
样本的选择思想是,认为领域内的信号是相似的,领域外的信号是需要区分的
正样本的选择:邻域的信号都是服从某个高斯分布,均值为t*,方差是窗口大小和邻域长度.领域内是正样本正样本。如果确定邻域,使用ADF检验。
负样本:不在邻域内的就是负样本,但是这一点,作者在损失函数里进一步优化了
损失函数:作者认为,不在一个领域不能都认为是负样本,因为时序问题具有周期性,因此应该把它归为正无标记样本(即正类和负类混合)。在处理上,根据PU学习的一些经验,它在上面的负样本中引入权重,同时进入损失函数。、
数据:总共3个数据:1个模拟数据(4个类别,HMM生成),1个医疗临床房颤数据(MIT-BIH,特点是类别交替进行,类别非常不平衡,少量个体(人)具体非常长的数据),1个人类活动数据(UCI-HAR数据)
下游任务:聚类与分类,其中主要目标是为了尽可能比较表征学习,因此对于同一任务,不同的模型都用了相同的,并且简单的编码器结构。由于不同数据集特点不一样,因此不同任务的编码器不同。
聚类用了简单的kmeans;分类用了简单的knn;本文的TNC都取得了最好的结果
arXiv,
2021.
DOI: 10.48550/arXiv.2106.00750
Abstract:
Time series are often complex and rich in information but sparsely labeled and therefore challenging to model. In this paper, we propose a self-supervised framework for learning generalizable representations for …
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Time series are often complex and rich in information but sparsely labeled and therefore challenging to model. In this paper, we propose a self-supervised framework for learning generalizable representations for non-stationary time series. Our approach, called Temporal Neighborhood Coding (TNC), takes advantage of the local smoothness of a signal's generative process to define neighborhoods in time with stationary properties. Using a debiased contrastive objective, our framework learns time series representations by ensuring that in the encoding space, the distribution of signals from within a neighborhood is distinguishable from the distribution of non-neighboring signals. Our motivation stems from the medical field, where the ability to model the dynamic nature of time series data is especially valuable for identifying, tracking, and predicting the underlying patients' latent states in settings where labeling data is practically impossible. We compare our method to recently developed unsupervised representation learning approaches and demonstrate superior performance on clustering and classification tasks for multiple datasets.
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919.
颜林林
(2022-09-21 07:48):
#paper doi:10.1002/humu.24458 Human Mutation, 2022, A survey of current methods to detect and genotype inversions. 倒位(inversion)是基因组上一类特殊的变异,越来越多的技术方法可以对其进行发现和鉴定,也因此发现该事件广泛存在于不同物种的基因组中。这篇综述从技术角度,分别介绍了PCR、NGS序列比对、单倍体型识别、模板链测序(template‐strand sequencing,Strand‐seq)、光学图谱(optical mapping,Bionano)及基因组组装这六类方法对倒位的鉴定,以及相应方法所取得的研究进展。
Abstract:
Polymorphic inversions are ubiquitous in humans and they have been linked to both adaptation and disease. Following their discovery in Drosophila more than a century ago, inversions have proved to …
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Polymorphic inversions are ubiquitous in humans and they have been linked to both adaptation and disease. Following their discovery in Drosophila more than a century ago, inversions have proved to be more elusive than other structural variants. A wide variety of methods for the detection and genotyping of inversions have recently been developed: multiple techniques based on selective amplification by PCR, short- and long-read sequencing approaches, principal component analysis of small variant haplotypes, template strand sequencing, optical mapping, and various genome assembly methods. Many methods apply complex wet lab protocols or increasingly refined bioinformatic analyses. This review is an attempt to provide a practical summary and comparison of the methods that are in current use, with a focus on metrics such as the maximum size of segmental duplications at inversion breakpoints that each method can tolerate, the size range of inversions that they recover, their throughput, and whether the locations of putative inversions must be known beforehand.
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920.
颜林林
(2022-09-20 06:54):
#paper doi:10.1002/humu.24465 Human Mutations, 2022, Long-read sequencing for molecular diagnostics in constitutional genetic disorders. 这是一篇关于使用三代长读长测序进行遗传病基因检测的综述,来自费城儿童医院。文章列举了其医院提供的耳聋基因检测的例子,来说明在实践中整合使用多种不同检测技术,实现检测上百个基因不同类型疾病相关突变的需求。此外,也通过实例,系统地分析了诸如重复片段、假基因、同一基因发生多个距离较远突变(需要进行phasing,即定相)等可能造成检测结果误判的问题,以及长读长测序技术如何解决相应问题。三代测序用于遗传基因检测,目前最大瓶颈在于所积累的证据和人群数据,但这正好是时间可以逐步积累并解决的。从这篇文章展示的这些几乎只能使用长读长相关技术才能解决的问题案例,可以预期不久的未来将迎来一批相应的长读长测序基因检测方法的落地应用。
Abstract:
Long-read sequencing (LRS) has been around for more than a decade, but widespread adoption of the technology has been slow due to the perceived high error rates and high sequencing …
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Long-read sequencing (LRS) has been around for more than a decade, but widespread adoption of the technology has been slow due to the perceived high error rates and high sequencing cost. This is changing due to the recent advancements to produce highly accurate sequences and the reducing costs. LRS promises significant improvement over short read sequencing in four major areas: (1) better detection of structural variation (2) better resolution of highly repetitive or nonunique regions (3) accurate long-range haplotype phasing and (4) the detection of base modifications natively from the sequencing data. Several successful applications of LRS have demonstrated its ability to resolve molecular diagnoses where short-read sequencing fails to identify a cause. However, the argument for increased diagnostic yield from LRS remains to be validated. Larger cohort studies may be required to establish the realistic boundaries of LRS's clinical utility and analytical validity, as well as the development of standards for clinical applications. We discuss the limitations of the current standard of care, and contrast with the applications and advantages of two major LRS platforms, PacBio and Oxford Nanopore, for molecular diagnostics of constitutional disorders, and present a critical argument about the potential of LRS in diagnostic settings.
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